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1.
Cell Tissue Bank ; 24(3): 535-549, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36454377

RESUMEN

One of the important issues in tissue engineering has been the development of 3D scaffolds, which guide cells to grow functional tissues and allow the diffusion of nutrients, metabolites, and soluble factors. Factors governing scaffold design include considerations of pore size and morphology, mechanical properties versus porosity, surface properties, and appropriate biodegradability. Three-dimensional structures with low density, high surface area and porosity can be utilized effectively in the tissue engineering. Recently two-nozzle electrospinning was used for fabricate polymeric and ceramic bulky layers with specific formulation. Fabrication of 3D carbon nanofiber with this method was investigated in this assay with FESEM, TGA-DTA, FTIR and XRD. Polyacrylonitrile was used as precursor. The collector speed was changed (15, 30, 60, 150, 300 and 450 rpm) to result in oriented 3D carbon nanofiber after stepwise thermal process under neutral gas atmosphere. The effect of the mechanical force applied by the collector rotation not only can arranged carbon fiber mat but also can change the crystallinity of the carbon structure. The viability and growth capability of cells on nanofibers towards the lowest cytotoxicity of them proved by MTT test. The growth characteristic of neural and mouse bone marrow mesenchymal stem cells cultured in the webs showed the good adhesion with the blown web relative to a normal electrospun mat. The electrospun nanofibers mat had good tensile properties and high porosity and provides a favorable environment for neural cell attachment and proliferation comparable to other scaffolds. The cell viability and cell growth capability in prepared nanofibers were assessed.


Asunto(s)
Nanofibras , Animales , Ratones , Nanofibras/química , Andamios del Tejido/química , Carbono , Poliésteres/química , Ingeniería de Tejidos/métodos , Proliferación Celular
2.
Mol Biol Rep ; 48(12): 7637-7646, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34741706

RESUMEN

BACKGROUND: Cancer is one of the most important reasons for mortality worldwide. Several synthetic products have shown valuable efficiency as an anticancer medicines. Chromene derivatives have long been used as the promising compounds which are potent in inhibition of the growth of tumors. METHODS AND RESULTS: In this study, we investigate an anticancer activity of barbituric/thiobarbituric acid-based chromene derivates. For this purpose, viability, antioxidant and apoptotic assays were conducted using three different cancer cell lines (A2780, MCF7, and A549). In most cases, the antiproliferative activity of barbituric acid-based derivatives was higher than that of thiobarbituric acid-based compounds. Among 14 compounds, compound 4g was the most potent one, which showed the highest effect on cells by increasing the accumulation of ROS (up to 540% increase), increasing the level of caspase-3 and caspase-9 (~ 35% increase), and decreasing the mitochondrial membrane potential (2.5 folds reduction). To characterize the type of cell death involved into our experiment Annexin V/PI double staining of compound 4g was performed. The results showed that the number of late apoptotic and/or necrotic cells (Ann V + /PI +) increased fourfold upon treatment with IC50 concentration of 4g. CONCLUSIONS: Overall, the anti-proliferative activity of barbituric acid-based derivatives was higher than that of thiobarbituric acid compounds, and compound 4g can be introduced as a potential candidate to prevent various cancers.


Asunto(s)
Barbitúricos/farmacología , Benzopiranos/farmacología , Neoplasias/tratamiento farmacológico , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Barbitúricos/química , Benzopiranos/química , Caspasa 3 , Caspasa 9 , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales/métodos , Humanos , Neoplasias/metabolismo , Especies Reactivas de Oxígeno , Relación Estructura-Actividad , Tiobarbitúricos/química , Tiobarbitúricos/farmacología
3.
Bioorg Chem ; 91: 103147, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31377390

RESUMEN

Ugi reaction was a reliable procedure for the synthesis of new coumarin-quinoline frameworks. Excellent yields, mild reaction conditions and easily available and inexpensive starting materials are advantages of this protocol. Cytotoxic effects of fourteen products were investigated in A2780 human ovarian cancer cells. Two synthesized compounds (L11 and L12) exhibited more anti-cancer activity than other derivatives with IC50 values of 0.042 mmol/L and 0.102 mmol/L, respectively and were thus selected for further studies. Apoptosis was induced through the intrinsic pathway by activating caspase 9 and ended at the executioner pathway of caspase 3. Measurement of intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were also carried out for both of them. Further studies on a mechanism by Real Time-PCR and Western blot analysis were performed for anti-apoptotic proteins Bcl-2 and survivin both in mRNA and protein level relating to the untreated A2780 cells. The treatment of A2780 cells with compound L11 significantly (P-value ≤ 0.05) induced apoptosis by down-regulation of Bcl-2 and survivin both in mRNA and protein level via a single dose (0.042 mmol/L), as well as activation of caspase 9 and 3, loss of MMP, and high ROS. Accordingly, findings supported the first report under which the pro-apoptotic activity of compound L11 as an apoptosis-inducing agent was related to mitochondrial-mediated dysfunction signaling pathways. Molecular docking supports experimental outcomes. Evidently, coumarin-quinoline scaffolds are potentially favorable options for further assessment as influential chemotherapeutic agents for the future.


Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Apoptosis , Benzopiranos/síntesis química , Benzopiranos/farmacología , Cumarinas/química , Mitocondrias/efectos de los fármacos , Neoplasias Ováricas/patología , Quinolinas/química , Femenino , Humanos , Potencial de la Membrana Mitocondrial , Mitocondrias/metabolismo , Simulación del Acoplamiento Molecular , Neoplasias Ováricas/tratamiento farmacológico , Especies Reactivas de Oxígeno/metabolismo , Células Tumorales Cultivadas
4.
Biotechnol Lett ; 36(11): 2271-4, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25048228

RESUMEN

The biotransformation of hydrocortisone (1) by Fusarium solani and Aspergillus ochraceus was investigated for the first time. After 10 days at 30 °C, just one metabolite was produced by both fungi: 11ß, 17α, 20ß, 21-tetrahydroxypregn-4-en-3-one (2) established on the basis of spectroscopic data. The reaction was reduction of the 20-carbonyl group. Time course study determined by HPLC showed 60 and 45 % yield for the metabolite by F. solani and A. ochraceus, respectively.


Asunto(s)
Aspergillus ochraceus/metabolismo , Fusarium/metabolismo , Hidrocortisona/análogos & derivados , Cetonas/química , Cetonas/metabolismo , Cromatografía Líquida de Alta Presión , Hidrocortisona/química , Hidrocortisona/metabolismo , Resonancia Magnética Nuclear Biomolecular
5.
J Microencapsul ; 31(3): 239-45, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24124881

RESUMEN

Methotrexate (MTX) widely used in the treatments of various types of malignancies, but high toxicity and short plasma half-life have limited its use. This study was aimed at developing a polymeric drug delivery system for improving the therapeutic index of this potent drug. To achieve these goals, PLGA and PLGA-PEG nanoparticles were prepared using the emulsification-solvent diffusion technique and were optimized for particle size and entrapment efficiency. The optimum loaded nanoparticles were evaluated by cytotoxicity and their ability to induce apoptosis compared to free drug by examining of caspase-3 activity. The results showed that optimized particles were 182 ± 14 nm and 258 ± 10 nm in size for PLGA-PEG and PLGA nanoparticles, respectively, with an entrapment efficiency of more than 51%. The cytotoxicity experiment showed that the nanoparticles were more effective than pure MTX and increase the activity of caspase-3 in MCF7 and AGS and A549 cell lines.


Asunto(s)
Antimetabolitos Antineoplásicos , Apoptosis/efectos de los fármacos , Ácido Láctico , Metotrexato , Nanocápsulas/química , Neoplasias/tratamiento farmacológico , Polietilenglicoles , Poliglactina 910 , Ácido Poliglicólico , Antimetabolitos Antineoplásicos/química , Antimetabolitos Antineoplásicos/farmacología , Caspasa 3/metabolismo , Línea Celular Tumoral , Citotoxinas/química , Citotoxinas/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Ácido Láctico/química , Ácido Láctico/farmacología , Metotrexato/química , Metotrexato/farmacología , Nanocápsulas/ultraestructura , Neoplasias/enzimología , Neoplasias/patología , Tamaño de la Partícula , Polietilenglicoles/química , Polietilenglicoles/farmacología , Poliglactina 910/química , Poliglactina 910/farmacología , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacología , Copolímero de Ácido Poliláctico-Ácido Poliglicólico
6.
Res Pharm Sci ; 19(4): 425-435, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39399724

RESUMEN

Background and purpose: Nowadays, herbal medicine has been utilized to treat various diseases such as cancer, which showed successful therapeutic efficacy in previous studies. This study for the first time evaluated the cytotoxic potential of cinnamaldehyde (CIN) alone and in combination with doxorubicin (DOX), a well-known potent anti-tumor agent, on the proliferation of prostatic cancer cell line (PC3). Experimental approach: The cytotoxicity and apoptotic activities of CIN and DOX, either separately or together, were determined on PC3 cells by the MTT test and Annexin V/PI assay, respectively. To further investigate which apoptotic pathway participated in cell death a collection of prominent markers of apoptosis induction including caspase-3/7 activations, mitochondrial membrane potential (MMP), and phosphatidyl serine translocation were detected. Findings/Results: The different concentrations of CIN and DOX significantly inhibited the proliferation of PC3 cells in a concentration-dependent way within a 24-h treatment. In addition, the induction of apoptosis by CIN was accompanied by an increase in the activation of caspase-3/7 in PC3 cells with IC50 concentrations of 12.5 and 10 µg/mL for CIN and DOX, respectively. Moreover, the morphological observations obtained from flow cytometry MMP and caspase-3/7 activity assays, altogether, revealed the potential effect of CIN on apoptosis induced in PC3 cells by DOX. Conclusions and implications: Taken together, the current study concluded that the combination of CIN and DOX could lead to the production of a potential therapeutic agent for prostate cancer. However, further in vivo and clinical studies are still needed to validate this combination in prostate cancer therapy.

7.
Int J Biol Macromol ; 279(Pt 4): 135425, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39245113

RESUMEN

Most conventional wound dressings do not meet the clinical requisites owing to their limited multifunctionality. Herein, a bilayer wound dressing containing both hydrogel and fibrous structures with multifunctional features was developed for effective skin rehabilitation. Sodium alginate (SA)/gelatin (Gel) hydrogel comprising Matricaria chamomilla L extract and silver sulfadiazine (AgSD) drug as antibacterial agents was cross-linked using genipin and CaCl2. Then, the surface of the hydrogel was covered by electrospun polyacrylonitrile (PAN) nanofibers to fabricate a bilayer dressing. FESEM images revealed formation of continuous, smooth, and bead-free PAN nanofibers with excellent compatibility between hydrogel and fibers. The bilayer wound dressing exhibited satisfactory mechanical virtues including elastic modulus (2.4 ± 0.2 MPa), tensile strength (6.2 ± 0.5 MPa) and elongation at break (21.8 ± 1 %) as well as suitable swelling ratio. Such bilayer dressing revealed biodegradability, cytocompatibility and effective antibacterial performance against gram positive and gram negative strains. Release kinetics of AgSD drug followed a Fickian diffusion mechanism, ensuring sustained drug release. In vivo studies demonstrated bilayer dressing could promote rate of wound closure, re-epithelialization and collagen deposition, facilitating the replacement of damaged skin with healthy tissue. Such engineered wound dressing has a high potency for inducing skin repair and could be used in skin tissue engineering.


Asunto(s)
Resinas Acrílicas , Alginatos , Antibacterianos , Hidrogeles , Extractos Vegetales , Sulfadiazina de Plata , Cicatrización de Heridas , Alginatos/química , Cicatrización de Heridas/efectos de los fármacos , Sulfadiazina de Plata/química , Sulfadiazina de Plata/farmacología , Resinas Acrílicas/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Vendajes , Animales , Manzanilla/química , Nanofibras/química , Humanos , Liberación de Fármacos , Ratones
8.
Iran J Pharm Res ; 23(1): e140666, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39005736

RESUMEN

This study assessed the acute and sub-chronic toxicity of Camelina oil, a well-known oil rich in polyunsaturated fatty acids that enhance cellular immunity and human health, in Wistar rats. Wistar rats, 5 per sex per group, were randomly assigned to three groups for acute (14 days) toxicity studies and five groups for sub-chronic (90 days) toxicity studies. In the acute study, Camelina sativa oil was administered orally at a single dose of 5000 mg/kg of body weight (BW). The positive control group received a single dose of 5 000 mg/kg BW Canola oil by gavage. In the sub-chronic study, Groups III-V received 250, 500, and 1 000 mg/kg BW of Camelina oil, while Groups I and II received ultra-pure water and Canola oil at a dose of 500 mg/kg BW, respectively. Throughout the experiment, clinical signs, mortality, and body weight were monitored. At the end of the sub-chronic study, hematological, biochemical, and histopathological investigations were conducted. Administration of Camelina oil and Canola had no significant effect on daily weight gain (P > 0.05) of the test rats. Serum calcium levels decreased while phosphorous levels increased in male rats treated with Camelina oil. Other hematological and biochemical parameters showed no significant differences or dose-response effects between control and seed oil groups in both sexes (P < 0.05). Moreover, in animal necropsy, there were no apparent lesions in the liver, heart, and kidney organs in any of the doses administered. In conclusion, the results suggest that oral administration of Camelina oil is unlikely to be toxic. Therefore, the possibility for the development of future human nutrition should be considered.

9.
Genome Biol ; 25(1): 44, 2024 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-38317241

RESUMEN

BACKGROUND: The androgen receptor (AR) is a tumor suppressor in estrogen receptor (ER) positive breast cancer, a role sustained in some ER negative breast cancers. Key factors dictating AR genomic activity in a breast context are largely unknown. Herein, we employ an unbiased chromatin immunoprecipitation-based proteomic technique to identify endogenous AR interacting co-regulatory proteins in ER positive and negative models of breast cancer to gain new insight into mechanisms of AR signaling in this disease. RESULTS: The DNA-binding factor GATA3 is identified and validated as a novel AR interacting protein in breast cancer cells irrespective of ER status. AR activation by the natural ligand 5α-dihydrotestosterone (DHT) increases nuclear AR-GATA3 interactions, resulting in AR-dependent enrichment of GATA3 chromatin binding at a sub-set of genomic loci. Silencing GATA3 reduces but does not prevent AR DNA binding and transactivation of genes associated with AR/GATA3 co-occupied loci, indicating a co-regulatory role for GATA3 in AR signaling. DHT-induced AR/GATA3 binding coincides with upregulation of luminal differentiation genes, including EHF and KDM4B, established master regulators of a breast epithelial cell lineage. These findings are validated in a patient-derived xenograft model of breast cancer. Interaction between AR and GATA3 is also associated with AR-mediated growth inhibition in ER positive and ER negative breast cancer. CONCLUSIONS: AR and GATA3 interact to transcriptionally regulate luminal epithelial cell differentiation in breast cancer regardless of ER status. This interaction facilitates the tumor suppressor function of AR and mechanistically explains why AR expression is associated with less proliferative, more differentiated breast tumors and better overall survival in breast cancer.


Asunto(s)
Neoplasias de la Mama , Factor de Transcripción GATA3 , Receptores Androgénicos , Femenino , Humanos , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Células Epiteliales/metabolismo , Factor de Transcripción GATA3/genética , Factor de Transcripción GATA3/metabolismo , Histona Demetilasas con Dominio de Jumonji/genética , Fenotipo , Proteómica , Receptores Androgénicos/genética
10.
Arch Pharm (Weinheim) ; 346(11): 812-8, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24123162

RESUMEN

In the current research of medicinal chemistry, apoptosis induction is one of the novel strategies for the development and discovery of novel anticancer therapeutics. In the present study, a new series of 1,3,4-thiadiazole derivatives (4a-4p) were synthesized and their in vitro anticancer activities were evaluated against three cancer cell lines: PC3 (prostate cancer), MCF7 (breast cancer), and SKNMC (neuroblastoma). These cell lines were utilized in MTT assays and the obtained results were compared to doxorubicin. Apoptosis induction was also investigated through exploration of the activation of caspases 3, 8, and 9. According to the obtained results, compounds 4b (3-Cl) and 4c (4-Cl) demonstrated the best caspase activation. In fact, compounds 4b and 4c enhanced the activity of caspases 3 and 9 in the MCF7 cell line.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Caspasas/metabolismo , Descubrimiento de Drogas , Activadores de Enzimas/farmacología , Neoplasias/enzimología , Tiadiazoles/farmacología , Antineoplásicos/síntesis química , Supervivencia Celular/efectos de los fármacos , Activación Enzimática , Activadores de Enzimas/síntesis química , Femenino , Humanos , Concentración 50 Inhibidora , Células MCF-7 , Masculino , Estructura Molecular , Neoplasias/patología , Relación Estructura-Actividad , Tiadiazoles/síntesis química
11.
Anticancer Agents Med Chem ; 23(14): 1634-1643, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37143273

RESUMEN

BACKGROUND/INTRODUCTION: 4-aryl-4H-chromenes have attracted attention as potential anticancer agents. OBJECTIVE: In an effort to discover effective compounds, we designed a new series of these chromenes with methoxy substitution at 2, 3, 4, 5, and 6 positions. METHODS: The synthesized compounds were tested for anticancer properties against two human cancer cell lines (MCF- 7 and PC3) as well as a normal cell line. Furthermore, induction of apoptosis was explored through various methods, such as flow cytometry analysis, morphological changes, activation of caspase 3, ROS, and MMP. RESULTS: The MTT assay showed that the 5g derivative, with methoxy groups at ortho and meta positions, exhibited the highest potency (IC50 = 40 µM) against the PC3 cell line. Our findings revealed that compound 5g induced apoptosis in the PC3 cell line, which was demonstrated by activation of caspase 3, an increase in ROS levels, and early apoptosis percentage. CONCLUSION: These results suggest that compound 5g holds promise as a potential therapeutic approach to cancer treatment.


Asunto(s)
Antineoplásicos , Benzopiranos , Humanos , Benzopiranos/farmacología , Relación Estructura-Actividad , Caspasa 3 , Línea Celular Tumoral , Especies Reactivas de Oxígeno , Ensayos de Selección de Medicamentos Antitumorales , Proliferación Celular , Antineoplásicos/farmacología , Apoptosis , Estructura Molecular
12.
Int J Biol Macromol ; 226: 1426-1443, 2023 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-36442567

RESUMEN

A polyamide/Pistacia atlantica (P.a) gum nanofiber, fabricated by electrospinning method, was coated on a layer of PEBAX/PVA hydrogel embedded with green synthesized Ag nanoparticles (AgNPs) and the prepared nanofiber-hydrogel composite was assessed for wound dressing application. The AgNPs were characterized using ultraviolet-visible (UV-Vis), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), transmission electron microscopy (TEM), and Zeta potential analysis. The PEBAX/PVA/Ag hydrogel, prepared using solution casting method, displayed strong mechanical properties as Young's modulus and the elongation at break for the hydrogel containing AgNPs increased by 12 % and 96 %, respectively. The PEBAX/PVA/Ag hydrogel showed a high antimicrobial activity towards the E. coli (22.8 mm) with no cytotoxicity. The effect of adding the P.a gum on the properties of polyamide nanofiber was investigated using FTIR, SEM, and tensile tests. Samples were assessed by swelling, degradation, and water vapor transfer measurements. Very fine and continuous fibers with average diameters of ≤200 nm were observed by SEM analysis due to the addition of the P.a gum. The result of tensile test indicated that the addition of P.a gum improves the mechanical properties of nanofibers. The physical properties and biocompatibility of the two layers were shown to be complementary when combined.


Asunto(s)
Antígenos de Grupos Sanguíneos , Nanopartículas del Metal , Nanofibras , Pistacia , Nanofibras/química , Nanopartículas del Metal/química , Hidrogeles/farmacología , Escherichia coli , Espectroscopía Infrarroja por Transformada de Fourier , Nylons , Plata/química , Alcohol Polivinílico/química , Vendajes , Antibacterianos/farmacología , Antibacterianos/química
13.
Artículo en Inglés | MEDLINE | ID: mdl-36095050

RESUMEN

Metal-fluoroquinolones have more antibacterial and cytotoxic effects compared to free fluoroquinolones. In this work, a bidentated Mn (II) complex with ofloxacin (MOC) was synthesized and its cytotoxicity activity, oxidative stress and DNA binding were studied. Anti- proliferative and cytotoxic tests revealed that MOC exhibits better anti proliferative and cytotoxic activities compared to OFL which was attributed to the more interaction of MOC with DNA. Therefore, the interaction of MOC with DNA was investigated by using voltammetry, UV-Vis, fluorescence, and in silico methods. The results revealed that MOC interacts with DNA via electrostatic and outside hydrogen binding via minor groove. The proposed DNA binding modes may support the greater in-vitro cytotoxicity of MOC compared to OFL alone.


Asunto(s)
Antibacterianos , Ofloxacino , Ofloxacino/farmacología , Antibacterianos/farmacología , Metales , ADN/metabolismo
14.
Curr Top Med Chem ; 23(23): 2242-2265, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37464828

RESUMEN

While food safety issues are attracting public concern due to their detrimental effects on human health, monitoring livestock health is urgently needed to diagnose animal diseases at an early stage by applying proper treatments, controlling, and preventing outbreaks, particularly in resource- limited countries. In addition, unhealthy farms are not only a threat to livestock but also to human lives. The available diagnostic techniques for the detection of key health threats within both the food and livestock sectors require labor-intensive and time-consuming experimental procedures and sophisticated and expensive instruments. To tackle this issue, optical biosensing strategies have been incorporated into point-of-care (POC) systems, offering real-time monitoring, field-deployable, and low-cost devices, which help make on-the-spot decisions. This review aims to discuss the recent cutting-edge research on POC optical biosensing platforms for on-farm diagnosis of animal diseases and on-site detection of animal-derived food-borne contaminants, including pathogens, antibiotics, and mycotoxins. Moreover, this review briefly presents the basic knowledge of various types of optical biosensors and their development using various recent strategies, including nanomaterial combinations, to enhance their performance in POC tests. This review is expected to help scientists to understand the evolution and challenges in the development of point-of-care biosensors for the food and livestock industry, benefiting global healthcare.


Asunto(s)
Enfermedades de los Animales , Técnicas Biosensibles , Animales , Humanos , Sistemas de Atención de Punto , Técnicas Biosensibles/métodos
15.
Iran J Med Sci ; 48(6): 551-562, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38094285

RESUMEN

Background: Despite suggesting many genetic risk markers as the outcome of Genome-wide association studies (GWAS) for breast cancer, replicating the results in different populations has remained the main issue. In this regard, this study assessed the association of two variations in Zinc Finger 365 (ZNF365) in an Iranian population. Methods: In a case-control study conducted at Mashhad University of Medical Sciences, Mashhad, Iran, between 2017 and 2020, ZNF365-rs10822013 and rs10995190 were genotyped using Allele-Specific PCR (AS-PCR). Breast density was assessed using mammography images. PHASE software module version 2 and SPSS version 16.0 were used for haplotype and statistical analyses. Quantitative and qualitative variables were compared between groups using independent t tests and Chi square tests, respectively. Binary logistic regression analysis was performed to calculate odds ratios. Multivariate analysis was then undertaken for the baseline variables, with a P<0.05 in the univariate analysis. The survival analysis was performed using the Kaplan-Meier method and the log-rank test. Results: In this survey, 732 females, including 342 breast cancer patients and 390 healthy subjects, were enrolled. rs10822013-T allele (P=0.014), rs10995190-G allele (P=0.003), and TG haplotype (P=0.002) were significantly associated with the increased risk of breast cancer. Moreover, rs10995190-GG genotype (P=0.042) and C-G haplotype (P=0.019) revealed a significant association with better overall survival. However, considered polymorphisms and their haplotypes indicated no association with breast density and clinical features of breast cancer. Conclusion: ZNF365 variants might be a potential risk marker of breast cancer in the Iranian population. The interaction between alleles in haplotypes may modulate the amount of the risk conferred by these variants. Further studies on different ethnic groups can validate these results.


Asunto(s)
Neoplasias de la Mama , Femenino , Humanos , Densidad de la Mama , Neoplasias de la Mama/genética , Estudios de Casos y Controles , Estudio de Asociación del Genoma Completo , Irán/epidemiología , Pronóstico , Dedos de Zinc
16.
Res Pharm Sci ; 17(1): 12-21, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34909040

RESUMEN

BACKGROUND AND PURPOSE: Doxorubicin (DOX) as a chemotherapeutic agent has been widely used in the treatment of various types of cancer. However, DOX exerts a toxic effect on normal tissues such as the brain. Furanocoumarins reduce the risk of cardiovascular and brain diseases because of their antioxidant activities. This study has been designed, for the first time, to evaluate the effect of known furanocoumarins oxypeucedanin and isoimperatorin extracted from Prangos ferulacea (L.) Lindl on oxidative stress and apoptosis induced by DOX toward pheochromocytoma cell line (PC12). EXPERIMENTAL APPROACH: NMR and MASS spectrometers were used to characterize the isolated compounds. The protective effects of isolated compounds on DOX-induced cytotoxicity in PC12 cells were examined by MTT assay. PC12 cells were pretreated with oxypeucedanin and isoimperatorin for 2 and 21 h, respectively, subsequently exposure to DOX at IC50 concentration. Then, mitochondrial membrane potential (MMP), Bax and Bcl2 mRNA expressions, caspase-3 activation, and the generation of intracellular reactive oxygen species (ROS) were measured after 24 h. FINDINGS/RESULTS: Pretreatment with oxypeucedanin and isoimperatorin significantly decreased DOX-induced apoptosis through reduction of caspase-3 activity and ROS generation and an increase in MMP. In addition, our finding showed pretreatment with these compounds leads to regulation of Bcl-2. CONCLUSION AND IMPLICATIONS: Taken together our observation indicated that oxypeucedanin and isoimperatorin have a protective effect against apoptosis induced by DOX in PC12 cells by inhibition of ROS production.

17.
Anticancer Agents Med Chem ; 22(13): 2439-2447, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35043767

RESUMEN

BACKGROUND: Isatin (1H-indole-2,3-dione) and its derivatives have been utilized in a variety of biological activities. Anticancer compounds were the most extensively highlighted and explored among the range of beneficial properties. OBJECTIVE: Herein, we report the targeting effect of halogenated isatin derivatives on cancer cell mitochondria and their antiproliferative mechanism. METHODS: A series of novel 5-halo-Isatin derivatives consisting of the 5-Amino-1,3,4-thiadiazole-2-thiol scaffold were synthesized and easily conducted in good yields through a condensation reaction between keto groups of Isatin and primary amine under alcoholic conditions, followed by S-benzylation. The compounds were fully characterized using spectroscopic methods such as 1H-NMR, FTIR, mass spectroscopy and then tested in vitro towards three cancer cell lines HT-29 (colon cancer), MCF-7 (breast cancer), and SKNMC (neuroblastoma). Apoptosis induction was investigated through assessment of caspase 3 and mitochondrial membrane potential. RESULTS: The most potent compounds of 5b, 5r (IC50 = 18,13 µM), and 5n (IC50 = 20,17 µM) were found to show strong anticancer activity, especially for MCF7 cells. Further anticancer mechanism studies indicated that 5b and 5r induced apoptosis through the intrinsic mitochondrial pathway. CONCLUSION: This research demonstrated that 5b and 5r have an anticancer property via the modulation of oxidative stress-mediated mitochondrial apoptosis and immune response, which deserves further studies on their clinical applications.


Asunto(s)
Antineoplásicos , Isatina , Antineoplásicos/química , Antineoplásicos/farmacología , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Isatina/química , Isatina/farmacología , Estructura Molecular , Relación Estructura-Actividad
18.
Anal Cell Pathol (Amst) ; 2022: 9725244, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35983460

RESUMEN

Results: Aqueous extract and essential oil reduced the viability of A549 cancer cells in a concentration-dependent manner. The lowest inhibitory concentrations (IC50) for both samples of D. ammoniacum oleo-gum resin were 10 and 2.5 µg/ml for 24 hours in A549 cell line, respectively. After treatment with extract and essential oil of D. ammoniacum oleo-gum resin, ROS increased significantly compared to the control group. Although changes in caspase-3 did not show a significant increase in extract, the caspase-3 was found to be increased after exposure to essential oil and caspase-9 was downregulated after exposure to essential oil. Also, exposure to essential oil of D. ammoniacum caused a reduction in MMP level. Conclusion: Based on results, the cytotoxic effect of essential oil of D. ammoniacum can induce apoptosis toward A549 cell line via induction of oxidative stress, MMP depletion, and caspase-3 activation, which is independent to mitochondrial cytochrome c release and caspase-9 function.


Asunto(s)
Neoplasias , Aceites Volátiles , Apoptosis , Caspasa 3/farmacología , Caspasa 9/farmacología , Línea Celular , Humanos , Aceites Volátiles/farmacología , Extractos Vegetales/farmacología
19.
ACS Omega ; 6(38): 24297-24303, 2021 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-34604613

RESUMEN

Rapid detection of single nucleotide variations (SNVs) is of critical importance to early diagnosis of several diseases and the prediction of diverse responses to a specific treatment. Based on the information published in the literature, discrimination of SNVs is a developing area of study with great research enthusiasm and is also an area that can benefit from microfluidics-integrated designs. This review provides a brief overview of different microfluidics-based strategies for rapid detection of SNVs and mismatched bases. Sensors based on various microfluidic formats, such as paper-based microfluidic biosensors, droplet-based microfluidic systems, and magnetic bead-based microfluidic biosensors, have been discussed with respect to their specific pros and cons for SNV detection. These systems have shown promise for distributed on-site diagnostics in personalized medicine.

20.
Spectrochim Acta A Mol Biomol Spectrosc ; 260: 119944, 2021 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-34020381

RESUMEN

The dose of administered chemotherapy drugs is crucial to determine due to the potential for efficient or adverse outcomes for cancer patients. To date, no user-friendly and low-cost method of doxorubicin (DOX) detection using nontoxic and biodegradable materials has been reported. For this reason, in this work, we have developed for the first time a nanofiber-based sensing platform for sensitive and on-site DOX assay in just 10 min. This is obtained thanks to printable, porosity and embeddability features of electrospun nanofibrous films (ENFFs) combined with nitrogen and sulfur co-doped carbon dots (NS-CDs) as sensing probes. The assay was done by just pipetting analyte on the hydrophilic spots of the fabricated photoluminescence water-stable ENFFs where the color intensity was being darkened. DOX quenched NS-CDs fluorescence onto ENFFs through inner filter effect. The developed sensor was either coupled with smartphone technology to provide miniaturized, portable and easy-to-use device or an ordinary spectrofluorimeter for solid-state sensing applications (detection limit of 5.4 nM). Moreover, applicability of the designed sensor was evaluated in human serum with satisfactory recoveries. It is more interesting that the fabricated NS-CDs/ENF scaffolds have a high potential to detect the intracellular DOX to enhance cell proliferation leading to be considered as a multimodal tool in biomedical research and clinical diagnostics.


Asunto(s)
Nanofibras , Puntos Cuánticos , Carbono , Colorantes Fluorescentes , Humanos , Nitrógeno , Teléfono Inteligente
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